Numerous studies from this laboratory have investigated the interaction of insulin with circulating mononuclear cells. We have attempted to characterize the insulin receptor of the human erythrocyte. Mononuclear cells and erythrocytes both have insulin receptors whose functions are altered by conditions of health and disease. Comparative studies of these two different cell types show that in some cases their insulin receptor status may be similar, but that the actual regulation of their receptor concentration may differ. The circulating monocyte is being used to study the function of alpha and beta subunit of the insulin receptor. One patient with insulin resistance shows discordance between insulin binding and insulin stimulated tyrosine-kinase activity. Six patients with Type A syndrome of insulin resistance shows concordance between insulin binding and insulin stimulated phosphorylation. The physiological role of receptor-associated tyrosine kinase activity remains unclear. The effects of sulfonylurea drugs on erythrocytes and monocytes in Type II diabetes are also under study. Further, it has been shown that the tumor promoting phorbol esters can stimulate tyrosine phosphorylation in circulating monocytes and in the U-937 monocyte cell line. This may represent an important link of these tumor promoters and polypeptide growth factors.